The targeted delivery via the circulation of liposomes encapsulating bioactive media like therapeutic or diagnostic substances towards selected areas in the organism combined with the assisted release of said substances at specific sites is attracting much attention in the medical field. For instance, N. Shoucheng et al., Int. J. Radiat. Oncol. Biol. Phys. 29 (1994), 827-834 have 25 disclosed injecting long lived liposomes (stealth) containing doxorubicine into the circulation of experimental animals and thereafter inducing controlled release of the doxorubicine at selected sites in the body via local hyperthermia induced by focused ultrasonic energy. Similarly, Bednarski et al. Radiology 204 (1997), 263-268 have disclosed the magnetic resonance guided targeting of liposome vesicles incorporating pharmaceuticals towards specific areas in the body, this being followed by the ultrasound controlled release into tissues of said pharmaceuticals, the effect being due to hyperthermialysis of the liposomal membrane.
In WO94/28873 and WO96/39079, there is disclosed a technique in which injectable targeted gas-filled microspheres, for instance gas-filled liposomes, comprising therapeutics embedded within the liposome bilayer membrane wall are directed to specific organs where they are caused to explode by ultrasonic irradiation in order to release said embedded therapeutic substances. It is difficult to incorporate drug into the gas filled liposomes (i.e. in the gas-phase or the surface membrane) without affecting their stability. If even a drug can be load in this kind of vesicles, it must be of a hydrophobic nature and the payload should be very low. Thus this method shows very limited practical utility. And also because after explosion, the therapeutic substance may stick some time to the constituents of the broken liposome membrane in which they were embedded, or the splintered parts of the liposome membranes may be simply "washed away" by the blood stream so that the active substance may not be released on the targeted site but elsewhere.
WO93/25241 discloses an ultrasound imaging technique in which a suspension of microspheres is targeted to organs of the body and caused to collapse under stimulation by ultrasonic energy, whereby a broad-band acoustic signal pulse is emitted and echo-detected by colour Doppler systems.
Although the techniques of the art have merit, a problem may arise due to the level of energy required to break the membrane of the liposomes and release the content thereof to a targeted area; if the area is located deep down in the body, the penetration of the energy beam into the body can have damaging effects to the intervening tissues. Hence searches have been undertaken to find a non-invasive energy releasing agent, closely associated with the liposome vesicles, which can innocuously help breaking the liposome membrane and release the trapped content thereof. In other words, it is strongly desired to make available an agent containing sufficient potential energy stored therein to open the liposome vesicles without harming the nearby or intervening tissues, said energy being liberated at will by external triggering means, so that the liposome encapsulated bioactive media be set free at a chosen site. The effect sought can be compared to that of a hypothetic prearmed spring to be remotely triggered and whose energy when released will cause the liposome content to be discharged at will. The present invention is set out to achieve this desired effect.